Arterio-venous shunt devices

ABSTRACT

A long-term implantable arterio-venous shunt device is provided that can be used as a therapeutic method. The shunt device is implanted between an artery and a vein, preferably between the aorta and the inferior vena cava. The shunt device decreases the systemic vascular resistance and allows a blood flow rate through the shunt device of at least 5 ml/min after the implantation. The blood flow rate could be controlled either via an open loop or a closed loop control means. The shunt device could also be a self-adjustable shunt device to self-adjust its structure to control the blood flow rate through its lumen. Based on the effects of the shunt device to the respiratory, cardiac and circulatory system, the implantable shunt device could be beneficial as a therapy to patients with problems or conditions related to these systems.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of and claims the benefitof currently pending U.S. application Ser. No. 10/820,169, filed 6 Apr.2004, which itself claims the benefit of U.S. Provisional Application60/461,467 filed 8 Apr. 2003, both of which are hereby incorporated byreference.

FIELD OF THE INVENTION

The present invention relates to implanted medical devices. Inparticular, the present invention relates to an arterio-venous shunt.

BACKGROUND

Chronic Obstructive Pulmonary Disease (COPD) is a syndrome that may becaused by a number of different diseases, all of which damage thealveoli and bronchioles, leading to impaired lung function. Thesediseases include including asthmatic bronchitis, chronic bronchitis(with normal airflow), chronic obstructive bronchitis, bullous disease,and emphysema. About 11% of the population of the United States hasCOPD, and according to the Mayo Clinic, COPD kills about 85,000 people ayear in the United States. As the alveoli and bronchial tubes aredestroyed, the remaining healthy lung tissue must work harder to providethe required amount of blood oxygenation. This need for more air leadsto lung over-inflation. As the lung over-expands, it gradually enlarges,completely filling the chest cavity and causing a sense of shortness ofbreath. The lung eventually looses its elasticity, and the combinationof a larger, less elastic lung and damaged, nonfunctioning tissue leadsto a slower air flow into and out of the lung, resulting in the feelingof an obstructed airway.

The present standard of care is oxygen therapy, which requires a patientto remain near a stationary oxygen source or carry a bulky portableoxygen source when away from home or a treatment facility. It is easy toappreciate that such oxygen therapy has many disadvantages.

Lung reduction surgery has recently been proposed for treating patientswith chronic obstructive pulmonary disease. Such surgery, however, isnot a panacea. It can be used on only a small percentage of the totalpatient population, requires long recovery times, and does not alwaysprovide a clear patient benefit. Even when successful, patients oftencontinue to require supplemental oxygen therapy.

It is desirable to provide improved approaches, including both devicesand methods, for treating patients suffering from chronic obstructivepulmonary disease and other related conditions.

SUMMARY OF THE INVENTION

The present invention encompasses implantable arterio-venous shuntdevices, and methods for using such devices for treating chronicobstructive pulmonary disease and other conditions, such as congestiveheart failure, systemic arterial hypertension, hypotension, respiratoryfailure, pulmonary arterial hypertension, lung fibrosis, adultrespiratory distress syndrome, and the like. The shunt device may beimplanted between an artery and a vein, for example between the aortaand the inferior vena cava.

The present invention diverts a portion of the patient's blood from thehigh-pressure arterial circulatory to the lower-pressure venouscirculatory system. This arterio-venous shunting has several effects,including increasing the mean or average partial pressure of bloodoxygen (paO₂) in a patient's circulation, increasing cardiac output, andreducing the mean arterial pressure. In the case of patients sufferingfrom chronic obstructive pulmonary disease, such increase in bloodoxygen relieves the shortness of breath and other symptoms suffered bythe patient.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic diagram showing a simplistic circulatory systemwith and without the shunt in place.

FIG. 2 is a schematic diagram showing blood flowing, with or without ashunt device of the present invention, from a high resistance arterialsystem with a high oxygen concentration to the low resistance venoussystem with a low oxygen concentration.

FIG. 3 is a schematic diagram showing a shunt device positioned betweenthe aorta and inferior vena cava.

FIG. 4 is a schematic diagram showing examples of shunt devices.

FIG. 5 is a schematic diagram showing shunt devices with a controlmeans.

FIG. 6 is a schematic diagram showing shunt devices with a controllableor self-adjustable flow regulator.

FIG. 7 is a schematic diagram showing shunt devices with a controllableflow-regulator mechanism suing a smart material.

FIG. 8 is a schematic diagram showing examples of a self-adjustableshunt devices and a graph according to the Poiseuille formula used todetermine change in pressure as a function of the length and radius ofthe shunt.

FIG. 9 is a schematic diagram showing a shunt device with a means toincrease resistance to blood flow.

FIGS. 10-12 show additional information regarding some physiologicaleffects of an arterio-venous shunt in rats according to the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides implantable arterio-venous shunt devices andmethods for using such devices. The shunts of the invention divert aportion of the patient's blood from the high-pressure arterialcirculatory system to the lower-pressure venous circulatory system. Theshunt device may be implanted between an artery and a vein, for examplebetween the aorta and the inferior vena cava. The shunts are adapted forimplantation into a human or animal subject for treating chronicobstructive pulmonary disease (COPD) and other, discussed below. Thearterio-venous shunting provided by these shunts has several importantphysiological effects, including increasing the mean or average partialpressure of blood oxygen (paO₂) in a patient's circulation, increasingcardiac output, and reducing the mean arterial pressure. In the case ofpatients suffering from chronic obstructive pulmonary disease, suchincrease in blood oxygen relieves the shortness of breath and othersymptoms suffered by the patient.

The shunt device may be adapted for implantation for an extended periodof at least 4 weeks, at least, or at least 3, 6, or 12 months, or evenfor a greater period of 3, 5, 7 or more years. Implantation may beachieved using standard open surgical procedures, or a minimallyinvasive surgical procedure, or an intravascular procedure.

The implantable arterio-venous shunt devices of the invention may beused to treat and alleviate the symptoms of various conditions, such aschronic obstructive pulmonary disease (COPD), congestive heart failure,systemic arterial hypertension, hypotension, respiratory failure,pulmonary arterial hypertension, lung fibrosis, adult respiratorydistress syndrome, and the like. Respiratory failure is a particularcondition that may be treated using the shunt of the invention.Respiratory failure is a condition characterized by a reduction inarterial oxygen concentration. The present invention treats respiratoryfailure by increasing the arterial oxygen content. Congestive heartfailure is a condition characterized by low cardiac output. Thisinvention treats heart failure by increasing the cardiac output.Systemic arterial hypertension is a condition characterized by a higharterial blood pressure. This invention treats systemic arterialhypertension by lowering the arterial blood pressure. Pulmonary arterialhypertension is a disease defined by an increase in pulmonary arterialpressure, which leads to reductions in cardiac output. This inventionwill increase venous oxygen concentration which in turn increases theoxygen content of the pulmonary arteries. The increased pulmonaryarterial oxygen content, combined with the increases in cardiac outputthat occur after the creation of the shunt, will lower the pulmonaryarterial pressure and increase the cardiac output in patients withpulmonary arterial hypertension. Pulmonary hypertension treatable by thepresent invention can occur (1) as a complication of a chronic hypoxia(low oxygen concentrations in arterial blood) which may be associatedwith chronic emphysema or chronic obstructive sleep apnea syndrome, (2)as a complication of left heart failure due to a variety of causesincluding mitral valve disease, (3) as a result of congenital heartdisease, and (4) as a compilation of abnormal increases in peripheralvascular resistance that are associated with familial pulmonaryhypertension, liver cirrhosis, HIV infection, systemic sclerosis,connective tissue diseases, and prior use of diet pills.

The present invention will simultaneously cause several distinctimprovements and effects on physiology: (1) an increased cardiac output(a benefit to patients with heart failure, who suffer low cardiacoutput), (2) a lower mean arterial blood pressure (a benefit to patientswith hypertension, whose blood pressure is too high), (3) a lowerdiastolic blood pressure (again a benefit to patients with hypertension,whose diastolic blood pressure is too high), (4) an increased arterialoxygen concentration (a benefit to both patients with heart failure andpatients with respiratory failure), and (5) a lower pulmonary arterialblood pressure (a benefit to patients with pulmonary hypertension, whosepulmonary arterial blood pressure is too high).

Methods according to the present invention for increasing the partialpressure of oxygen (paO₂) in circulating blood generally comprisecreating a shunt to divert oxygenated arterial blood to a venouscirculatory location. The amount of oxygenated arterial blood divertedmay be selected based on several different criteria. In a firstinstance, the amount of blood diverted through the shunt may be selectedto increase mean arterial paO₂ (MAP) by at least 5% compared to meanarterial paO₂ prior to the shunt creation, preferably by at least 10%,or at least 15% or at least 20%, and often by 30% or greater.Alternatively, and often in the case of patients suffering fromhypertension, the amount of blood diverted may be selected to lower meanarterial blood pressure by at least 5% compared to arterial bloodpressure prior to the shunt creation, usually by at least 10%, or atleast 15% or at least 20%, or at least 30% or greater. A third criteria,often useful for patients suffering from congestive heart failure, willbe to create the shunt to divert oxygenated arterial blood in an amountsufficient to increase mean cardiac output by at least 5% compared tomean cardiac output prior to shunt creation, often increasing cardiacoutput by at least 10%, by at least 15%, or at least 20% or at least30%, or at least 50% or greater. Alternatively, and often in the case ofpatients suffering from pulmonary arterial hypertension, the amount ofblood diverted may be selected to lower mean pulmonary arterial bloodpressure by at least 5% compared to the pulmonary arterial bloodpressure prior to the shunt creation, usually by at least 10%, or atleast 20%, and often at least 30% or greater.

The shunt will typically be implanted via an open surgical procedure,via a minimally invasive surgical procedure, via an intravascularprocedure, or the like. The particular procedure or method will dependon the specific arterial and venous locations which are to be connectedby the shunt or shunt.

The present invention further provides a circulatory therapy comprisingcreating a shunt between an arterial location and a venous location. Theparticular arterial and venous locations will be selected to provide therelatively high blood flow volumes which are preferred or required toachieve the therapeutic effects of the present invention. For example,the presently preferred arterial location is the aorta (eithersupra-renal or infra-renal) and venous location is the inferior venacava (IVC) which can provide the desired blood flow volumes and islocated close to the heart so that the diverted blood is quicklyreturned to the heart and lungs for further oxygenation. Other exemplaryand preferred arterial and venous locations include: axillary artery andvein, the common iliac artery and vein, the external iliac artery andvein, the internal iliac artery and vein, the femoral artery and vein,the subclavian artery and vein.

The present invention further provides a circulatory therapy comprisingdiverting oxygenated arterial blood to a venous location, where theamount of blood diverted is controlled in response to a measuredphysiological parameter. A measured physiological parameter will usuallybe selected to reflect the condition of the patient who is beingtreated. For example, a measured parameter may be blood oxygen partialpressure (paO₂) in patients suffering from chronic pulmonary obstructivedisease or respiratory failure due to other causes, or may be arterialblood pressure in patients suffering from systemic arterial hypertensionor may be hypotension, may be cardiac output and/or heart rate inpatients suffering from CHF, or may be may be pulmonary arterialpressure or pulmonary vascular resistance in patients with pulmonaryarterial hypertension.

The amount of arterial blood which is diverted may be controlled by aflow control element in the shunt device implanted between the arterialblood location and the venous location. Control may be effected byparticular devices including valves, pumps, controllable orifices,multiple orifices, tapering lumens, and the like. The physiologicparameters may be measured periodically or in real time. For example,the methods comprised periodically adjusting a valve or other flowcomponent when a patient visits a patient's physician who can make theappropriate measurements. Alternatively, the measurements may be madereal time by implantable sensors which control a coupled flow element.

The present invention also provides devices. Shunts according to thepresent invention are preferably adapted to connect a location in ahuman aorta (either supra-renal or infra-renal) to a location in a humaninferior vena cava to create a conduit through which blood may pass.Usually, the shunt has a lumen with a cross-sectional area in the rangefrom 3, 5, 6, 8, or 10 mm² to 3000 mm², preferably from 20 mm² to about1000 mm² or alternatively from 40 mm² to about 750 mm² or alternativelyfrom 75 mm² to 500 mm², typically from 90 mm² to 300 mm², or from 100mm² to 250 mm², or from 150 mm² to 200 mm², depending on the rate offlow desired. The lumen of the shunt device may have a length in therange from 3 mm to 20 mm, 30 mm, 50 mm, or 100 mm or more, depending onthe proximity of the artery and the vein, typically from 5 mm to 10 mm.

Shunts according to the present invention are capable of carrying fromabout 5 ml/min or 25 ml/min or 50 ml/min to about 5000 ml/min of bloodat a pressure differential of 70 mmHg, typically from 150 ml/min to 1500ml/min, and usually from 300 ml/min to 750 ml/min. Such shunts typicallycomprise a body having a lumen and in some embodiments a flow controlelement in the lumen. The flow control element may be a one-way controlvalve, typically where the valve opens at a differential pressure in therange from 50 mmHg to 130 mmHg, for example at a pressure of about 50mmHg, about 75 mmHg, about 100 mmHg or about 130 mmHg. Alternatively,the flow control element may be a flow control valve which may beconnected to a pressure-responsive or other controller. Furtheralternatively, the flow control element may be a pump.

The inner wall of the shunt lumen will generally be smooth to preventturbulence, and in certain embodiments may be coated with varioussubstances such as Teflon to produce an even surface not liable toencourage clot formation, deposition of proteins and other substancesand to prevent biofouling of the lumen.

In some embodiments it may be desirable to control the blood flow ratethrough the shunt. For this purpose a control means may be provided. Thecontrol means may be a simple on/off mechanism such as a valve orswitch, or it could comprise a more sophisticated system includingeither an open loop control or a closed loop control with feedbackprovided by physiological parameters such as blood pressure and flowrate. For each level of sophistication, the control means could includea controller (ranging from a switch to a decision algorithm), one ormore flow control elements that control the rate of flow through thelumen, and/or one or more sensors to provide feedback to a controller.Examples of physiological parameters that could be sensed or measure areblood pressure, heart rate, cardiac output, paO₂, O₂ saturation, O₂saturation, mean systemic arterial pressure or mean systemic venouspressure.

In an alternate embodiment, the shunt device is a self-adjustable shuntdevice that automatically and inherently self-adjusts its crosssectional area or its length, or both, as a function of the pressuredifference across the shunt device. The self-adjustable shunt could thenautomatically control the blood flow rate through the shunt at apredetermined blood flow rate level or range.

The reduction of systemic vascular resistance and (controlled) bloodflow through the shunt device from the arterial system to the venoussystem has physiological consequences on respiratory, cardiac andcirculatory systems. In certain embodiments, the invention includes arespiratory or cardio-respiratory therapy producing an increase of thepartial pressure of O₂ dissolved in the arterial blood plasma, anincrease of the hemoglobin O₂ saturation in arterial or venous blood, oran increase of the O₂ concentration in arterial or venous blood. Inanother embodiment may include a therapy to encourage increased cardiacoutput. In yet another example, the method could be a circulatorytherapy to decrease the pulmonary arterial blood pressure, a decrease ofthe systemic arterial blood pressure, a decrease of the systemicsystolic pressure or a decrease of the systemic diastolic pressure.Patients with circulatory problems could benefit from such a circulatorytherapy.

In use, the shunt creates allows blood flow from the arterial system tothe venous system while bypassing peripheral microcirculation. Bloodflow through a lumen of the device typically results on a pressuregradient between the blood in the arterial system to the blood in thevenous system, indicated by the large P and small p in FIG. 1. While thepressure gradient between the arterial and venous sides of thevasculature will generally be sufficient to achieve and control thetarget volume of blood flow, in some instances it may be desirable toutilize a pump or other flow inducing device in order to increase orcontrol the blood flow. Simple pumps include positive displacementpumps, such as rotary pumps, peristaltic pumps, and the like.

In general, the shunt device may be positioned between any non-cardiacartery and vein, usually an adjacent vein. In one embodiment, the deviceis positioned between the aorta and the inferior vena cava. In anotherembodiment, the device is positioned distal from the renal arteries. Thedevice could be positioned in the pelvis to link the common iliac arteryand vein, or femoral artery and vein. In another embodiment the devicecould be positioned in the axilla where it would link the axillaryartery and vein. In yet another embodiment the device could bepositioned close to the clavicle and link the subclavian artery andvein.

The shunt device could be made from any biocompatible material that isstrong enough or reinforced sufficiently to maintain a lumen sufficientto provide the desired blood flow volume. In one embodiment, the shuntdevice is made of metal, preferably titanium, surgical steel, or anickel-titanium alloy (NiTi), while in other embodiments the devicecould be formed from conventional vascular graft materials. The innersurface of the lumen which conducts blood is preferably coated in wholeor in part to inhibit the formation of blood clots. The surface could becoated with for instance polytetrafluoroethylene (Teflon®), or the like.The device might also be coated with antibiotic to prevent infection,and/or anti-proliferative agents to prevent clot formation in the lumen.

The cross-sectional area of the lumen of the shunt device will beselected to provide a desired volumetric blood flow rate between thearterial vasculature and the venous vasculature. Typically, the lumenwill have a circular cross section and a diameter in the range from 1 mmto 30 mm, typically from 2 mm to 10 mm, for example 4 mm to 6 mm. Thelength of the shunt device will also affect the flow resistance and thusthe flow rate through the shunt. Typically, the shunt may have a lengthin the range from 3 mm to 60 mm, typically from 10 mm to 40 mm, forexample, 20 mm to 30 mm. In some instances, of course, it may bepossible to implant two or more shunt devices at different locationsbetween the arterial and venous sides of the vasculature. In cases ofsuch multiple shunt device implantations, the individual shunts may beimplanted in close proximity to each other or may be distributed atdifferent regions of the vasculature. The examples herein generallyfocus on the case where only a single shunt device has been implanted toprovide the entire volume of arterial blood into the venous side of thevasculature.

The cross-sectional area of the shunt device lumen will be selected toprovide a volumetric blood flow which in turn may be selected so thatthe heart beats at a reasonable and sustainable rate. As a person ofaverage skill in the art would recognize, a diameter of the lumen thatresults in a heart rate of, for instance, 170 beats per minute would notbe sustainable and should be avoided by selecting a smaller diameter.Usually, the target heart rate will be in the range from 80 to 140 beatsper minute, more usually from 90 to 110 beats per minute.

FIG. 1 is a schematic diagram of the general circulation without (110)and with (120) the device in place. Blood is pumped from the heart viathe arterial system (AS) to the vasculature of the tissues from which itreturns to the heart via the venous system (VS) as shown by system.Blood returning to the right side of the heart is pumped to the lungswhere it becomes oxygenated before returning to the left side of theheart to be pumped to the body's tissues via the arterial system. Bloodflow experiences a resistance from all of the systemic vasculature,which is referred to as the systemic vascular resistance (SVR). The SVRexcludes the pulmonary vasculature. The SVR plus the pulmonaryvasculature resistance Is referred as total peripheral resistance (TPR).

The present invention decreases the SVR by having an arterio-venousshunt device 130 implanted to shunt and re-circulate blood from thearterial system to the venous system in system 120. The blood directedthrough the shunt 130 bypasses the peripheral circulation and thereforedecreases the SVR. FIG. 1 shows a schematic diagram of a system with ashunt (120) and a system without a shunt (110) where SVR₁ is lower thanSVR₀. A desirable decrease of the SVR would be at least about 5% afterthe implantation of shunt device 130.

In general, shunt device 110 could be implanted between a large(proximal) artery and a large (proximal) vein. The location is selectedto shunt blood from the high resistance arterial system with a highoxygen concentration to the low resistance venous system with a lowoxygen concentration as shown by system 120 in FIG. 2. In a preferredembodiment, implantation of shunt device 130 is between the aorta 310and the inferior vena cava 320, either proximal of the renal arteries,or more preferably distal of the renal arteries, as shown in FIG. 3.

Blood flow through a lumen 230 of the shunt device 130 results from apressure gradient between the blood in the arterial system and the bloodin the venous system, indicated by the large P and small p in FIG. 2. Ina preferred embodiment, the blood flow rate through shunt device is atleast about 5 ml/min. While the pressure gradient between the arterialand venous sides of the vasculature will generally be sufficient toachieve and control the target volume of blood flow, the blood flowcould also be regulated by a pump mechanism such as a spiral rotary pumpmechanism or any other pump mechanism available in the art. In additionto the size of the lumen, the blood flow through the lumen could nowalso be a function on the speed of operation of the internal pumpmechanism. The pump mechanism could also be electrically charged usingan internal battery or by external power using a magnetic impeller, bothof which are common techniques in the art.

With respect to the cardiac effects, an important consequence ofdecreasing the systemic vascular resistance (SVR) is that the cardiacoutput increases according to:

${CO} = {\frac{{MAP} - {CVP}}{SVR} \times 80}$

whereby CO is cardiac output, MAP is mean arterial pressure, and CVP iscentral venous pressure. Since CVP is normally near 0 mmHg, thecalculation is often simplified to:

${CO} = {\frac{MAP}{SVR} \times 80}$

Cardiac output is equivalent to the blood flow rate according to:

CO=SV*HR

whereby SV is stroke volume and HR is heart rate.

When SVR decreases, MAP decreases to a smaller degree. The decrease inMAP is due to a small drop in systolic pressure (P_(systolic)) and alarger drop in diastolic pressure (P_(diastolic)). P_(diastolic) isdependent on the SVR whereby a drop in SVR results in a drop inP_(diastolic). The pulse pressure (P_(systolic)−P_(diastolic)) is thenincreased. For instance, before implantation MAP could be 90 mmHg andSVR could be 18 dynes, which results in a CO of 5 liters per minute. SVRof 18 dynes is determined by dividing an SVR of 1440 dynes by aconversion factor of 80. MAP of 90 mmHg is determined by using:

${MAP} \cong {P_{diastolic} + {\frac{1}{3}( {P_{systolic} - P_{diastolic}} )}}$

with an exemplary PP of 30 mmHg given a P_(systolic) of 110 mmHg andP_(diastolic) of 80 mmHg.

After implantation, SVR could for instance drop from 1440 dynes to 1000dynes and with the conversing factor of 80 drop from 18 to 12.5. Ifblood pressure has a P_(systolic) of 100 mmHg over a P_(diastolic) of 55mmHg, then MAP is 70 mmHg; i.e. in this example the P_(systolic) couldhave dropped by 10 mmHg, but the P_(diastolic) could have dropped by 25mmHg. Combining these exemplary numbers would result in a cardiac outputof 5.6 liters per minute; i.e. 70 mmHg divided by 12.5.

With respect to the respiratory effects, an important consequence ofshunting arterial blood to the venous circulation (such as the aorta tothe inferior vena cava) is that blood with high O₂ content circulates tothe venous blood system without having the O₂ extracted in tissuecapillaries. The O₂ “rich” arterial blood re-circulates to, and mixeswith, the low O₂ concentration of the venous system. As a result, theblood flowing through shunt device 130 increases the O₂ concentration inthe venous blood, which is illustrated by the different (font) sizes ofO₂ in FIG. 2. The increase of O₂ concentration in the venous bloodsystem leads to an increase in the O₂ concentration in the arterialblood in two ways, which is also illustrated by the different (font)sizes of O₂ in FIG. 2. First, since the blood that is shunted does nothave O₂ extracted by tissue capillaries, the blood returning to thelungs has a higher O₂ concentration after the creation of the shunt thanbefore. Second, O₂ is carried in the blood in two forms: (i) dissolvedin arterial plasma, and (ii) bound to a protein called hemoglobin thatis contained in red blood cells. Oxygen binds to hemoglobin withcurvilinear kinetics, so that O₂ very efficiently binds to (and iscarried by) hemoglobin at high PaO₂ (partial pressure of O₂ in arterialplasma), but when the PaO₂ is low (in particular below a PaO₂ of 60mmHg), O₂ is less efficiently bound to (or carried by) hemoglobin. Sincethe amount of O₂ that is bound to hemoglobin is related to the PaO₂, anincrease in PaO2 will result in greater binding of O₂ to hemoglobin, andincreased oxygen carrying capacity.

With respect to circulatory effects, an important consequence ofdecreasing SVR is related to the fact that the lungs regulate theirblood flow according to the O₂ content. A low O₂ content in the smallpulmonary arteries impairs blood flow to the lung resulting in a highpulmonary pressure—a process called hypoxic pulmonary vasoconstriction.Therefore increasing the O₂ content in the pulmonary arterial bloodshould decrease the pulmonary arterial blood pressure. Other importantcirculatory consequences, as described supra with respect to cardiacconsequences, are a decrease in systemic arterial blood pressure, adecrease in systemic arterial systolic pressure and/or a decrease insystemic arterial diastolic pressure.

As a person of average skill in the art would readily appreciate, thedifferent distinct effects could be beneficial to patients with cardiacproblems as a cardiac therapy, to patients with respiratory problems asa respiratory or cardio-respiratory therapy, or to patients withcirculatory problems as a circulatory therapy. An illustrative list oftherapies is for instance:

Cardiac therapies. The shunt device of the present invention couldbenefit patients with cardiac failure or patients who suffer from a lowcardiac output (congestive heart failure) by providing an increasedcardiac output.

Respiratory or cardio-respiratory therapies. The shunt device of thepresent invention could benefit patients with pulmonary arterialhypertension to lower pulmonary arterial blood pressure, patients withheart and/or respiratory failure by increasing arterial oxygenconcentration, patients with chronic obstructive pulmonary disease byincreasing of blood oxygen concentration.

Circulatory therapies: The shunt device of the present invention couldbenefit patients with hypertension to lower systemic arterial, systolicand/or diastolic blood pressure.

Other diseases or conditions that could benefit from the presentinvention are, for instance, hypotension (by increasing cardiac output),lung fibrosis, adult respiratory distress syndrome, and the like.

The blood flow rate through the shunt device is preferably at least 5ml/min. In case the shunt device is a cylinder then the parameters ofthe lumen of the shunt device that determine the blood flow rate throughits lumen can be determined with the Poiseuille equation:

${BFR} = \frac{{\pi\Delta}\; \Pr^{4}}{8\; \eta \; l}$

whereby the volume flow rate (BFR) is a function of a blood withviscosity η, the pressure difference ΔP across the lumen of the shuntdevice, length l of the lumen of the shunt device and radius r of thelumen of the shunt device as shown by shunt device 410 in FIG. 4. Onecould also refer to the cross sectional area CSA of the lumen of shuntdevice 410, which is in case of a cylinder equivalent to πr². Generallyspeaking, the shape of the lumen could be a circle, an oval or any othershape as long as the requirement of blood flow is met.

In an illustrative example using the Poiseuille equation, ΔP could rangefrom about 30 mmHg (in someone with a MAP of 40 mmHg and a venouspressure of 10 mmHg) to about 150 (in someone with a MAP of 160 mmHg anda venous pressure of 10 mmHg). The blood viscosity could be determinedin a variety of ways that could for instance be obtained from a paper byJohnston B M et al. (2004) entitled “Non-Newtonian blood flow in humanright coronary arteries: steady state simulations” and published in JBiomechanics 37:709-720. With a viscosity of 0.0345P and a combinationof a radius of 3 mm and a length of 3 mm of the lumen of the shuntdevice one would achieve a blood flow rate through the shunt of over 5ml/min. As a person of average skill would readily appreciate, differentcombinations of radius and length could be determined to achieve thedesired blood flow rate. In general, the length could range from about2.5 mm to about 15 mm, and the radius could range from about 2.5 mm toabout 15 mm. For the length one could determine a minimum length of e.g.2.5 mm given an exemplary wall thickness of a human adult aorta of about1.5 mm and an exemplary wall thickness of a human adult inferior venacava of about 1 mm. One could also express the lumen opening in terms ofcross section area, which could range from about 19 mm² to about 750mm².

The shunt device is preferably made from any biocompatible materialstrong enough or sufficiently reinforced to maintain a lumen that meetsthe desired blood flow rate. In one embodiment, the shunt device is madeof metal, preferably titanium, while in other embodiments the shuntdevice could be formed from conventional vascular graft materials,polytetrafluoroethylene (PTFE), nickel titanium memory, elasticmaterial, or the like. The inner surface of the shunt device ispreferably coated in whole or in part to inhibit the formation of bloodclots. The surface could be coated with for instancepolytetrafluoroethylene (Teflon®), or similar coatings/products. Theshunt device might also be coated with antibiotic to prevent atheroma,infection, and/or anti-proliferative or anticoagulant agents to preventclot formation in the lumen.

A secure connection between the shunt device and the artery and vein isdesirable. Different techniques could be employed to provide such asecure connection. For instance, for attachment of shunt devices formedfrom typical fabric graft materials one could use sutures, staples,biocompatible glues, or the like. In the case of metals and other rigidmaterials, the shunt device could be formed with flared or flanged ends,such as the umbrella or funnel device 424 (shown in FIG. 4). Umbrellaends 424 are placed at opposite ends of a tubular element 422 that formshunt device 420. Umbrella ends 424 are positioned respectively insidethe artery and inside the vein, and the tubular element connects inbetween the artery and the vein. In a different embodiment, umbrellaends 434 could be positioned more or less perpendicular with respect totubular element 432 as shown in shunt device 430. The key idea is thatthe diameter of the securing (connection) elements is larger than theopening in the artery and vein thereby keeping the shunt device inplace. The securing elements could include a mechanism that unfolds whenthe shunt device is in place and implanted in the artery and vein. Theart teaches different techniques and securing type mechanisms that couldbe used in the present invention.

The shunt device(s) could be implanted in a variety of ways, includingthe open surgical procedures, the laparoscopic and other minimallyinvasive techniques, and the intravascular techniques (where all or aportion of the shunt device is introduced at least partially through thelumen of one of the blood vessels to be shunted). The shunt device couldalso be implanted by, for instance, a surgical procedure such as anaortic surgery. The shunt device could further be implanted throughinterventional procedures such as, for instance, by means of a catheterthrough the iliac artery and guided by fluoroscopy. The shunt devicecould be deployed over a guidewire (e.g. the Seldinger technique) andassembled in the body through interventional radiology techniques likethe opening of an umbrella. All such surgical and interventionaltechniques are well known in the art. It is preferred to leave the shuntdevice implanted in the person for a long-term period (at least 6 weeks,but most often for years).

In some cases it might be desired to include a control means to controlthe blood flow rate with one or more flow control elements, one or morecontrollers and/or one or more sensors. A flow control element 520 couldbe placed in the shunt device 510 as shown in FIG. 5. It could be placedat either end of the shunt device or somewhere in between. In oneexample, the function of the flow control element could be as simple asto have an electrically, magnetically or mechanically open/closemechanism such as a switch or one-way valve. Such an open/close elementcould also be a hook with a lever or a gearshift. In another example, acontroller 530 could be used to control the timing of opening/closing(e.g. frequency and duration) or to control changes in blood flow rate.Controller 530 could control flow control element 510 such as one-wayvalve(s), pump(s) (positive displacement pump(s), rotary pump(s),peristaltic pump(s), and the like), controllable orifice(s) and thelike. The flow control element could be electrically charged using aninternal battery (e.g. a lithium battery; not shown) or by externalpower (not shown) using a magnetic impeller, both of which are commontechniques in the art.

Yet another advancement of the control means for the shunt device is toinclude one or more sensors 540 that provide feedback to the controller530. The figures show two sensors, however, the present invention is notlimited to two sensors and could be at least one sensor that isimplanted inside the shunt device, near the shunt device, or inside ornear the vasculature system. The sensor(s) could also be placed outsidethe body. Sensors 540 could sense (and/or measure) physiologicalparameter(s) in real time either periodically or continuously. Theselection of one or more physiological parameters could be to reflectthe condition of a person or patient who is being treated. Examples ofphysiological parameters that could be sensed with one or more sensorsare blood pressure, heart rate, cardiac output, paO₂, O₂ saturation, O₂saturation, mean systemic arterial pressure, and/or mean systemic venouspressure. The controller could include a decision method to determineappropriate action on the flow control element. The controller couldeither be a stand-alone implantable controller and/or could be operatedfrom outside the body. It might be useful to update the controller orchange the current controller settings; e.g. in cases when thecontroller controls a set-value, a particular range or criticalboundaries (minima/maxima), or when the controller requires an upgradeof its code.

The controller may select different criteria that are e.g. dependent onthe type of disease, condition and/or desired therapy. In one example,the heart rate could be maintained at a reasonable physiological rangeand not exceed the person's maximum heart rate. The controller couldhave a target heart rate range of, for instance, 80 to 140 beats perminute, more usually from 90 to 110 beats per minute. In anotherexample, it might be desired to increase cardiac output, partialpressure of O₂ dissolved in the arterial blood plasma (PaO₂), thehemoglobin O₂ saturation in arterial or venous blood, or the O₂concentration in arterial or venous blood. These increases could be atleast 5% compared to their value before implantation, except for HbO₂,which could be at least 1%. In a preferred situation these increasescould be higher and on the order of 10% or 20% and up (5% and 10% forHbO₂). In still another example, it might be desired to decrease thepulmonary arterial blood pressure, the systemic arterial blood pressure,the systemic systolic pressure or the systemic diastolic pressure. Thesedecreases could be at least 5% compared to their value beforeimplantation.

In a preferred situation these decreases could be higher and on theorder of 10% or 20% and up. In yet another example, the blood flow ratecould increase from at least 5 ml/min compared to before implantation toa situation where the shunt is capable of carrying up to 5000 ml/min ofblood at e.g. a pressure differential across the shunt device of 70mmHg.

The description supra relates to a shunt device whereby the blood flowrate could be changed and controlled. In these situations, thestructural parameters of the shunt device, such as the length, crosssection area and radius are fixed. However, in an alternate embodiment,described infra, the shunt device could change its cross section area,radius and/or length. This could be accomplished either in a controlledfashion, like with a controller and sensor(s) as described supra, or ina self-adjustable fashion (i.e. self-organizing fashion).

FIG. 6 shows an example of a shunt device 610, 620 with a mechanism ofleaves 630 disposed in the lumen of the shunt device that could changethe cross section area of the lumen. Leaves 630 could be attached to acentral axis or to the inner wall of shunt device 610, 620 respectively.Two or more leaves could be used with the capability of changing theirposition from a closed position gradually to an open position (compare610 and 612, and 620 and 622 respectively). The leaves in shunt devices610, 620 could be integrated with a controller 640 and/or sensor(s) 650in a similar fashion as described supra.

Leaves 630 could also be included as a self-adjusting mechanism foropening and closing of the shunt device. When the blood flow increasesor blood pressure increases, the flexible leaves automatically open upfrom a more or less closed position to a more or less open position, andvice versa.

FIG. 7 shows an example of a shunt device 710 that is made of a smartmaterial such as a memory metal/alloy that can change its length andcross sectional area (radius). For instance, shunt device 710 could bemade longer as shown by 720 or wider as shown by 730 (larger crosssectional area). Shunt devices 710 could be integrated with a controller740 and/or sensor(s) 750 in a similar fashion as described supra.Mechanisms of memory metals/alloys (including particular stent-graftmaterials) and their controls are known in the art.

In a self-adjustable fashion it could e.g. be desirable to keep theblood flow rate at a level or range across the shunt device without anycontroller; i.e. the shunt device is self-organizing. To establish thisthe length and radius need to work in tandem as a function of ΔP andaccording to the Poiseuille equation (see supra) (see FIG. 8). Forinstance, length and ΔP have a linear relationship such that when ΔPincreases the length increases in a linear fashion to maintain the bloodflow rate at the same level, and vice versa. The radius and ΔP have aninverse non-linear relationship such that when ΔP increase the radiusdecreases in a non-linear fashion to maintain the blood flow rate at thesame level, and vice versa. It is pointed out that the length and radiushave to work in opposite and unequal value to maintain a particularblood flow rate (see supra for Poiseuille equation). Shunt device 810should then be made of a material that is capable of increasing itslength, but simultaneously decreasing its radius when ΔP increases,(indicated by changing from 810 and 820). Examples of such materials areelastic materials with reinforced filaments or fibers arranged anddistributed over (or within) the shunt device (not shown in 810, 820) toensure selected and directional changes, according to Poiseuilleequation; i.e. (i) an increase in cross sectional area with a decreasein length, and (ii) a decrease in cross sectional area with an increasein length.

Other than following the Poiseuille equation one could change the bloodflow rate by following Ohm's law by increasing the resistance to bloodflow through the shunt device. Means to increase this resistance couldfor instance be accomplished by disposing roughness or obstacles such asbumps 930 or filaments/spokes 940 to the inner wall of the lumen ofshunt device 910, 920 respectively as shown in FIG. 9. The blood flowcould then also change from laminar flow to non-laminar flow.

FIGS. 10-12 show additional information regarding some physiologicaleffects of an aorto-caval shunt in rats. These effects are the result ofa study performed by the inventors of the present invention. FIG. 10shows the effect of an aorto-caval shunt on several groups ofexperimental animals. In each group the presence of an aorto-caval shuntwas associated with increased aortic blood flow (AF) and with increasedpartial pressure of oxygen in arterial blood (PaO₂) in rats that werereceiving supplemental oxygen (FiO₂=0.24, or the fraction of inspiredoxygen was 24%). Measurements of: (A): Aortic flow (24% O₂) and (B):Arterial blood oxygen tension (FiO₂=0.24) (PaO₂). Note that groups PMand PFM received FiO₂=0.50 during experimentation. Group N representsnormal rats (n=6), Group F underwent aorto-caval shunt (n=6), Group Punderwent left pneumonectomy (n=6), Group PF underwent leftpneumonectomy and the creation of an aorto-caval shunt (n=6), Group Mreceived a toxin that causes pulmonary hypertension called monocrotaline(n=6), Group FM underwent aorto-caval shunt and received monocrotaline(n=6), Group PM underwent left pneumonectomy and received monocrotaline(n=6), Group PFM underwent left pneumonectomy and the creation of anaorto-caval shunt and then received monocrotaline (n=6). (**=p<0.01).

FIG. 11 shows the effect of the presence of an aorto-caval shunt inseveral groups of experimental animals. Aorta-caval shunta attenuatesthe development of pulmonary arterial hypertension. The measurementsshown in FIG. 11 are of mean pulmonary artery pressures (PAP). Group Nrepresents normal rats (n=6), Group F underwent aorto-caval shunt (n=6),Group P underwent left pneumonectomy (n=6), Group PF underwent leftpneumonectomy and the creation of an aorto-caval shunt (n=6), Group Mreceived monocrotaline (n=6), Group FM underwent aorto-caval shunt andreceived monocrotaline (n=6), Group PM underwent left pneumonectomy andreceived monocrotaline (n=6), Group PFM underwent left pneumonectomy andthe creation of an aorto-caval shunt and then received monocrotaline(n=6). (*=p<0.05, **=p<0.01).

FIG. 12 shows photomicrographs of small pulmonary arteries (A-D). (A)shows an example that normal rat (group N) arterioles do not haveevidence of neointimal formation (grade 0). (B) shows an example of agrade 1 neointimal lesion (<50% occlusion) seen in rats that receivedmonocrotaline alone (group M). (C) shows an example of grade 1neointimal lesion (<50% occlusion) seen in rats that underwent leftpneumonectomy and the creation of an aortocaval shunt (ACF) and thenreceived monocrotaline (group PMF). (D) shows an example of a grade 2neointimal lesion (>50% occlusion) seen in rats that underwent leftpneumonectomy and received monocrotaline (group PM). Allphotomicrographs (×400), elastin van Gieson stain.

The present invention has now been described in accordance with severalexemplary embodiments, which are intended to be illustrative in allaspects, rather than restrictive. Thus, the present invention is capableof many variations in detailed implementation, which may be derived fromthe description contained herein by a person of ordinary skill in theart. For example, in some instances, it may be possible and desirable toimplant two or more shunt devices at different locations between thearterial and venous sides of the vasculature. In cases of such multipleshunt device implantations, the individual shunts may be implanted inclose proximity to each other or may be distributed at different regionsof the vasculature.

In another aspect, it should be pointed out that the present inventioncould be used as preventative care or as a therapy for a condition ordisease. Furthermore, as a person of average skill would readilyappreciate, the long-term implantable shunt device could be beneficialto improve the performance in athletes, military service personnel,performance animals (e.g. dogs and horses).

The preferred location of the shunt device is between the aorta andinferior vena cava as described supra. However, it would be feasible toimplant one or more shunt devices for a long-term period in the pelvisarea to link the common iliac artery and vein or femoral artery andvein. In another embodiment the shunt device could be positioned in theaxilla and it would link the axillary artery and vein. In yet anotherembodiment the device could be positioned close to the clavicle and linkthe subclavian artery and vein.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined only by the claimsand any amendments thereto.

1. A therapeutic method for treating a human subject, the methodcomprising: (1) selecting a human subject suffering from at least onecondition selected from: chronic obstructive pulmonary disease,congestive heart failure, systemic arterial hypertension, hypotension,respiratory failure, pulmonary arterial hypertension, lung fibrosis, andadult respiratory distress syndrome, (2) implanting an arterio-venousshunt device between an artery and vein of said subject, wherein saidshunt device is adapted to divert a portion of the subject's blood fromthe arterial circulatory system to the venous circulatory system, andwherein implantation of said shunt device results in a decrease of thesystemic vascular resistance and an increase in the cardiac output insaid subject.
 2. The method of claim 1, wherein said artery and saidvein are selected from the group consisting of iliac artery and vein,femoral artery and vein, axillary artery and vein, and subclavian arteryand vein.
 3. The method as set forth in claim 1, wherein said thearterio-venous shunt device has a length from about 2.5 mm to about 15mm.
 4. The method as set forth in claim 3, wherein said respiratory orsaid cardio-respiratory therapy is based on an increase of the partialpressure of O₂ dissolved in the arterial blood plasma, an increase ofthe hemoglobin O₂ saturation in arterial or venous blood, or an increaseof the O₂ concentration in arterial or venous blood.
 5. The method asset forth in claim 1, wherein said method is a cardiac therapy.
 6. Themethod as set forth in claim 5, wherein said cardiac therapy is based onan increase of the cardiac output.
 7. The method as set forth in claim1, wherein said method is a circulatory therapy.
 8. The method as setforth in claim 7, wherein said circulatory therapy is based on adecrease of the pulmonary arterial blood pressure, a decrease of thesystemic arterial blood pressure, a decrease of the systemic systolicpressure or a decrease of the systemic diastolic pressure.
 9. The methodas set forth in claim 1, further comprising controlling said blood flowrate through said shunt device at a blood flow rate level or range. 10.The method as set forth in claim 9, wherein said controlling furthercomprises sensing and using physiological parameters, wherein saidphysiological parameters are blood pressure, heart rate, cardiac output,paO₂, O₂ saturation, O₂ saturation, mean systemic arterial pressure ormean systemic venous pressure.
 11. The method as set forth in claim 1,further comprising self-adjusting said blood flow rate through saidshunt at a predetermined blood flow rate level or range by having saidshunt device capable of self-adjusting its cross sectional area or itslength, or both, as a function of the pressure difference across saidshunt device.
 12. The method as set forth in claim 1, wherein said shuntdevice is implantable via an open surgical procedure, a minimallyinvasive surgical procedure, or an intravascular procedure.
 13. Anapparatus for therapy in a human, comprising: a long-term implantablearterio-venous shunt device adapted for placement between an artery anda vein in said human to divert a portion of the blood from the arterialcirculatory system to the venous circulatory system to decrease thesystemic vascular resistance, wherein the cross sectional area and thelength of the lumen of said shunt device are selected to having a bloodflow rate through said shunt device of at least 5 ml/min after saidimplantation.
 14. The apparatus as set forth in claim 13, wherein saidartery is an aorta and said vein is an inferior vena cava.
 15. Theapparatus as set forth in claim 13, wherein said cross sectional area isin the range of about 19 mm² to about 750 mm²
 16. The apparatus as setforth in claim 13, wherein said length is in the range of about 2.5 mmto about 15 mm.
 17. The apparatus as set forth in claim 13, wherein theradius is in the range of about 2.5 mm to about 15 mm.
 18. The apparatusas set forth in claim 13, further comprising a control means to controlsaid blood flow rate through said shunt at a blood flow rate level orrange.
 19. The apparatus as set forth in claim 18, wherein said controlmeans comprises one or more sensors to sense said blood flow rate or thepressure difference across said shunt device.
 20. The apparatus as setforth in claim 18, wherein said control means comprises one or more flowcontrol elements.
 21. The apparatus as set forth in claim 13, whereinsaid shunt device is a self-adjustable shunt device to self-adjust itscross sectional area or its length, or both, as a function of thepressure difference across said shunt device to automatically controlsaid blood flow rate through said shunt at a predetermined blood flowrate level or range.
 22. The apparatus as set forth in claim 13, whereinthe inner wall of said shunt device has a coating to prevent clotformation or atheroma formation.
 23. (canceled)
 24. (canceled)